These studies are directed towards an examination of some of the proposed physiological roles of prostaglandins, particularly in terms of the regulation of the renal circulation. Since preliminary evidence suggests that the intrarenal actions of prostaglandins are coupled to those of kallikrein-kinins and are reciprocally related to those of the renin-angiotensin system, we will measure simultaneously changes in the activity of each. In addition to monitoring continuously, using the blood superfused-organ technique, changes in release from an organ of prostaglandin-like substances, we will use solvent extraction and thin- layer chromatography, coupled with parallel bioassay to measure changes in concentrations of prostaglandins of the E("PGE") and F("PGF") series: sensitivity 0.02 and 0.04 ng/ml, respectively. The effects of inhibitors of prostaglandin synthesis, previously identified by preventing conversion of C14-arachidonic acid to prostaglandins in renal hemogenates, on efflux of prostaglandins from the kidney will be related to changes in renal blood flow, its distribution and excretory functions in chloralose-anesthetized dogs and in the isolated blood-perfused dog kidney. Changes in cardiac output, vascular resistances in several organs, and the activity of renin and kallikrein of renal origin will also be related to the primary effects of inhibition of prostaglandin synthetase. Statistical treatment will include Dunnett's test to determine the effect of an intervention on the experimental kidney, and correlation coefficients and analyses of covariance to determine possible relationships between simultaneous functions. These studies may define an intrarenal vasodilator-diuretic system which normally affects vascular tone and reactivity, and salt and water excretion. abnormalities of this system may determine some forms of hypertension and may determine the onset of states associated with disorders of salt and water excretion.